WO2005000985A2 - Phenol antimicrobien contenant des compositions de cyanoacrylate - Google Patents

Phenol antimicrobien contenant des compositions de cyanoacrylate Download PDF

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Publication number
WO2005000985A2
WO2005000985A2 PCT/US2004/017573 US2004017573W WO2005000985A2 WO 2005000985 A2 WO2005000985 A2 WO 2005000985A2 US 2004017573 W US2004017573 W US 2004017573W WO 2005000985 A2 WO2005000985 A2 WO 2005000985A2
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WO
WIPO (PCT)
Prior art keywords
composition
cyanoacrylate
cyanoacrylate ester
blend
weight percent
Prior art date
Application number
PCT/US2004/017573
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English (en)
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WO2005000985A3 (fr
Inventor
Ian A. Askill
Herbert H. Gary
A. Sidney Finkelstein
Original Assignee
Medlogic Global Limited
Medtech Products, Inc.
Rezsofi, Michael, J.
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Application filed by Medlogic Global Limited, Medtech Products, Inc., Rezsofi, Michael, J. filed Critical Medlogic Global Limited
Publication of WO2005000985A2 publication Critical patent/WO2005000985A2/fr
Publication of WO2005000985A3 publication Critical patent/WO2005000985A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
    • C09J4/00—Adhesives based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; adhesives, based on monomers of macromolecular compounds of groups C09J183/00 - C09J183/16
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

  • This invention is directed to methods and formulations for the treatment or prevention of infections on mammalian tissues such as skin. Specifically, the methods of this invention involve the in situ formation of a polymeric cyanoacrylate film over mammalian tissue wherein the film comprises an antimicrobially effective amount of phenol.
  • iodophors are also insoluble in the cyanoacrylate composition thereby necessitating thorough mixing of the composition immediately prior to application. That is to say that during the normal shelf-life of the composition, the insoluble iodophor suspended in the composition will fall out of suspension thereby necessitating mixing of the composition immediately prior to use.
  • incorporation of an iodophor to the composition transforms the composition from clear or transparent to a reddish solution. When applied to skin, the reddish formed polymer layer can be unsightly.
  • cyanoacrylate compositions have been disclosed for use in a variety of medical environments such as an alternative or adjunct to sutures 2 or as a hemostat 3 .
  • Other described uses of cyanoacrylate prepolymers include their use on mammalian tissue to form polymeric films that are utilized:
  • compositions having enhanced shelf-life would provide for easy to use products over prolonged periods of time.
  • phenol has long been known to act as a polymerization inhibitor for cyanoacrylate adhesives 10
  • the specific use of phenol as an antimicrobial agent in topical medical applications and the resulting synergistic stabilizing effect in cyanoacrylate prepolymeric compositions was not previously known.
  • the suitability of phenol as an antimicrobial agent in topical adhesives is also surprising as phenol is a known caustic agent and it was unknown if extended contact with a tissue would result in tissue irritation and/or incompatibility with other conventional additives employed in the composition.
  • cyanoacrylate adhesive compositions comprising polymerizable cyanoacrylate ester, phenol, polymerization inhibitors, and an optional biocompatible plasticizer. These compositions are useful in methods for covering mammalian tissue and, in particular, mammalian skin with a polymeric antimicrobial film that may reduce the risk of infection to the underlying and/or adjacent tissue and, in the case of mammalian skin, may form a waterproof film over the skin.
  • the invention described herein is also directed, in part, to methods for the treatment or prevention of infections in mammalian tissue which methods involve formation of an antimicrobial cyanoacrylate polymeric film over mammalian tissue by the in situ polymerization of the cyanoacrylate adhesive composition.
  • This composition can be applied as a liquid/gel to the tissue surface and can include additional therapeutic agents such as analgesics, anti-inflammatory agents, and the like.
  • the cyanoacrylate adhesive compositions described herein generally include a polymerizable cyanoacrylate component; a phenol component, in an amount sufficient to provide effective antimicrobial activity; polymerization inhibitors, in amounts sufficient provide inhibition or retardation of polymerization prior to the use of the composition; and an optional biocompatible plasticizer component, in an amount sufficient to provide enhanced flexibility for the resulting film coating formed by polymerization of the cyanoacrylate adhesive composition.
  • the composition comprises: (a) a polymerizable cyanoacrylate ester; (b) about 0.01 to about 5 weight percent phenol based on the total weight of the composition; (c) about 100 to about 3,500 ppm of polymerization inhibitors; and (d) optionally from about 10 to about 30 weight percent based on the total weight of the composition of a biocompatible plasticizer.
  • a polymerizable cyanoacrylate ester comprising: (a) a polymerizable cyanoacrylate ester; (b) about 0.01 to about 5 weight percent phenol based on the total weight of the composition; (c) about 100 to about 3,500 ppm of polymerization inhibitors; and (d) optionally from about 10 to about 30 weight percent based on the total weight of the composition of a biocompatible plasticizer.
  • the composition employs a blend of different cyanoacrylate esters in order to provide greater flexibility and wear durability, such as taught in Berger, et al., U.S. Patent No. 5,998,472.
  • a particularly preferred mixture comprises about 1.5:1 to about 2:1 mixture of ?7-butyl cyanoacrylate and octyl cyanoacrylate (e.g., 2-ethylhexyl cyanoacrylate).
  • Another preferred mixture comprises about 1.5:1 to about 2:1 mixture of w-butyl cyanoacrylate and decyl cyanoacrylate.
  • the composition also preferably employs a blend of polymerization inhibitors, with blends of hydroquinone (HQ) and sulfur dioxide being preferred, and blends of hydroquinone, 4-methoxyphenol, and sulfur dioxide being most preferred. In a particularly preferred embodiment, these inhibitors are employed in a 4:4:1.5 ratio.
  • HQ hydroquinone
  • sulfur dioxide hydroquinone
  • these inhibitors are employed in a 4:4:1.5 ratio.
  • the cyanoacrylate adhesive compositions described herein may be used for the treatment or prevention of infections on mammalian tissues, particularly mammalian skin.
  • the method comprises: (a) applying to bacterially infected mammalian tissue or mammalian tissue at risk of bacterial infection an amount of a cyanoacrylate adhesive composition sufficient to form an adherent polymeric film on the tissue where the composition was applied upon polymerization of the cyanoacrylate adhesive composition.
  • the polymerizable cyanoacrylate ester component of the composition generally contains one or more cyanoacrylate ester monomers.
  • R is selected from the group consisting of: alkyl of 1 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, cycloalkyl groups of from 5 to 8 carbon atoms, phenyl, 2-ethoxyethyl, 3-methoxybutyl, and a substituent of the formula: R' O
  • R' wherein each R' is independently selected from the group consisting of: hydrogen and methyl, and R" is selected from the group consisting of: alkyl of from 1 to 6 carbon atoms, alkenyl of from 2 to 6 carbon atoms, alkynyl of from 2 to 6 carbon atoms, cycloalkyl of from 3 to 8 carbon atoms, aralkyl selected from the group consisting of benzyl, methylbenzyl and phenylethyl, phenyl, and phenyl substituted with 1 to 3 substituents selected from the group consisting of hydroxyl, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms, and alkoxy of from 1 to 4 carbon atoms.
  • R is alkyl of from 2 to 10 carbon atoms and even more preferably alkyl of from 2 to 8 carbon atoms. Still more preferably, R is butyl, pentyl or octyl.
  • the cyanoacrylate ester component contains a blend of two different cyanoacrylate monomers.
  • One preferred blend that may be used contains a mixture of n-butyl cyanoacrylate and octyl cyanoacrylate, with 2-ethylhexyl cyanoacrylate being the preferred octyl cyanoacrylate.
  • the polymerized cyanoacrylate composition has a thickness of no more than about 1 millimeter and, more preferably, the polymer layer has a thickness of from about 2 to about 500 microns and still more preferably about 20 to about 1 00 microns.
  • This invention is directed to methods and formulations for the treatment or prevention of infections on mammalian tissues such as skin.
  • this invention is not limited to any particular composition, reactable cyanoacrylate ester, or biocompatible plasticizer, as such may vary. It is also to be understood that unless terms are specifically defined the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.
  • alkyl refers to monovalent alkyl groups of 1 to 10 carbon atoms, which may be straight chained or branched, and include, for example, methyl, ethyl, propyl (-CH 2 CH 2 CH 3 or -CH(CH 3 )CH 3 ), n-butyl, and the like.
  • alkynyl refers to monovalent straight or branched chain alkyl groups having from 2 to 10 carbon atoms and more preferably 2 to 6 carbon atoms and having at least 1 and preferably from 1-2 carbon-carbon triple bonds.
  • cycloalkyl refers to a cyclized alkyl ring containing from 3 to 10 ring atoms, preferably 5 to 8 ring atoms and more preferably, 5 to 6 ring atoms.
  • the cycloalkyl group may optionally be substituted with from 1 to 3 alkyl groups.
  • Cycloalkyl is also intended to cover alkyl substituted cycloalkyl groups where the point of attachment to the core molecule is through the alkyl group on the cycloalkyl ring.
  • alkoxy refers to O-alkyl groups where alkyl is defined as herein.
  • aralkyl refers to -alkyl-aryl groups where alkyl and aryl are as defined herein. And this group is exemplified for example by benzyl, phenethyl, and the like.
  • Aryl or “Ar”, as used herein, refers to an unsarurated aromatic carbocyclic group of from 6 to 14 carbon atoms having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings may or may not be aromatic (e.g., benzo[l,3]dioxole-6-yl, benzo[b]thiophen-5-yl, chroman-4-one-6-yl, and the like) provided that the point of attachment is on an aromatic carbocyclic group.
  • Preferred aryls include phenyl and naphthyl.
  • biocompatible refers to a material that, in the amounts used, is substantially non-toxic and substantially non-irritating when applied to tissue.
  • cP as used herein refers to a centipoise and is equivalent to a centistoke
  • antimicrobially effective amount refers to an amount of an antimicrobial agent sufficient to ameliorate the symptoms of, prevent the symptoms of, or delay the progression of a microbial infection or other ailment.
  • the Cyanoacrylate Adhesive Composition generally contain a polymerizable cyanoacrylate ester component, phenol, a polymerization inhibitor or mixture of inhitors, and an optional biocompatible plasticizer. Below is a detailed description of the amounts and types of the different components that may be used. [0041] Specifically, the adhesive compositions of the invention exhibit one or more of the following: enhanced antimicrobial properties, increased stability (as indicated by increased shelf-life), increased flexibility, increased adherence to mammalian skin an/or superior wear durability.
  • the Polymerizable Cyanoacrylate Ester Component contains one or more cyanoacrylate monomers or polymerizable cyanoacrylate oligomers. In their monomeric form the cyanoacrylate monomers are preferably compounds represented by formula I as described above.
  • the polymerizable cyanoacrylate ester component preferably comprise from about 50 to about 99.9 weight percent of the total weight of the adhesive composition, more preferably about 50 to about 99.5 weight percent of the total weight of the adhesive composition and even more preferably from about 75 to about 99.5 and still more preferably from about 75 to about 89.5 weight percent of the total weight of the adhesive composition.
  • R is preferably an alkyl group from 2 to 10 carbon atoms including but not limited to ethyl, ⁇ -propyl, iso-propyl, ..-butyl, iso-butyl, sec-butyl, n- pentyl, iso-pentyl, «-hexyl, iso-hexyl, 2-ethylhexyl, «-heptyl, octyl, nonyl, and decyl.
  • R is butyl, pentyl or octyl and most preferably, R is «-butyl or octyl, with octyl most preferably being 2-ethyl hexyl.
  • Mixtures of such compounds can also be employed as disclosed by Berger, et al., U.S. Patent No. 5,998,472, which is incorporated herein by reference in its entirety.
  • the polymerizable cyanoacrylate composition contains a blend of n-butyl cyanoacrylate and octyl cyanoacrylate.
  • the ratio of r ⁇ -butyl cyanoacrylate ester to octyl cyanoacrylate ester in this preferred blend preferably ranges from about 1.5 : 1 to about 2: 1 (w/w). It has been found that this blend of cyanoacrylate esters provides improved flexibility to the resulting polymerized film and increases the adhesion and wear durability of the polymeric film. [0046] In an alternative preferred embodiment, a blend of /.-butyl cyanoacrylate and decyl cyanoacrylate may be used. The preferred ratio of r ⁇ -butyl cyanoacrylate ester to decyl cyanoacrylate ester ranges from about 1.5 : 1 to about 2: 1 (w/w).
  • this blend of cyanoacrylate esters also provides improved flexibility, increased adhesion, and enhanced wear durability to the resulting polymeric film.
  • a blend of r ⁇ -butyl cyanoacrylate and ethoxyethyl cyanoacrylate may be used.
  • the preferred ratio of -butyl cyanoacrylate ester to ethoxyethyl cyanoacrylate ester ranges from about 1:1 to about 2:1 (w/w).
  • the polymerizable cyanoacrylate ester components described herein rapidly polymerize in the presence of water vapor or tissue protein and bond to mammalian skin tissue without causing histotoxicity or cytotoxicity.
  • the polymerizable cyanoacrylate ester component may contain one or more known cyanoacrylate ester monomers.
  • Phenol [0050] Generally, the of phenol in the cyanoacrylate adhesive composition is an antimicrobially effective amount and is a non-toxic amount. Using the teachings in this patent and techniques well known in the art, one of skill in the technology described herein would find it straightforward to determine the range of antimicrobially effective amounts of phenol and the range of non-toxic amounts of phenol. For example, measurements of minimum inhibition concentrations (MIC) or the measurement of zones of inhibition (ZOI) conferred by the films of this invention would be useful. All phenol amounts described here are as weight percentages of phenol based on the total weight of the composition.
  • MIC minimum inhibition concentrations
  • ZOI zones of inhibition
  • Ranges of amounts of phenol that may be used include from about 0.01% to about from about 0.01% to about 5%, from about 0.1% to about 1.4%, from about 0.1% to about 1.0%, from about 0.5% to about 1.0%, from about 0.6% to about 1.0% and from about 0.1% to about 0.6%. Phenol concentrations may also be as low as about 0.005%.
  • the inventors have experimentally demonstrated or are led to believe by their experimental results combined with their knowledge of the technology that these ranges of phenol provide the above- discussed synergistic antimicrobial/stabilizin effect. While the use of phenol as an antimicrobial agent has been suggested by others, the synergistic stabilizing effect was not present in the adhesives so suggested.
  • phenol is a known caustic agent and is not recommended for extended contact with bare skin, it has surprisingly been found that cyanoacrylate adhesive formulations of this invention are substantially non-irritating and are suitable for use in these formulations.
  • the Polymerization Inhibitor [0052]
  • the cyanoacrylate adhesive compositions described herein also contain about 100 to about 3,500 ppm of polymerization inhibitor (s).
  • the polymerization inhibitor(s) is (are) present in amounts effective to inhibit premature polymerization of the composition during storage.
  • the term "inhibiting amount" of a polymerization inhibitor means an amount of the polymerization inhibitors effective to prevent premature polymerization during storage.
  • Suitable polymerization inhibitors include a mixture of anionic polymerization inhibitors and free radical polymerization inhibitors.
  • a preferred version of this polymerization inhibitor blend includes 400 ppm hydroquinone, 400 ppm 4-methoxyphenol, and 150 ppm sulfur dioxide. This particular blend has been found to provide a highly stable cyanoacrylate adhesive when used in conjunction with the phenol antimicrobial agent. In another preferred embodiment, 2000 ppm butylated hydroxyanisol (BHA) and 150 ppm sulfur dioxide are used.
  • BHA butylated hydroxyanisol
  • Preferred concentration ranges for anionic polymerization inhibitors, in such mixtures of adhesive composition range from about 50 ppm to about 500 ppm.
  • anionic polymerization inhibitors include, but are not limited to, sulfur dioxide, sulfonic acids, sulfuric acid, sulfur trioxide. phosphorous acids, carboxylic acids, picric acid, boron trifluoride, and hydrogen fluoride.
  • Free radical polymerization inhibitors included in mixtures containing blends with anionic polymerization inhibitors are present in concentrations ranging from about 50 to about 3000 ppm.
  • suitable free radical polymerization inhibitors include, but are not limited to, hydroquinone, 4-methoxyphenol, butylated hydroxyanisol (BHA), and butylated hydroxy toluene (BHT).
  • Such additional inhibitors include very strong acids that have an aqueous pK a of less than 1.0.
  • Suitable very strong acidic inhibitors include, but are not limited to, very strong mineral and/or oxygenated acids. Examples of such very strong acids include, but are not limited to, sulfuric acid (pK a -3.0), perchloric acid (pK a -5), hydrochloric acid (pK a -7.0), hydrobromic acid (pK a -9), fluorosulfonic acid (pK a ⁇ -10), chlorosulfonic acid (pK a -10).
  • Such additional inhibitors also include acids with higher pKa than the acids described above and may be provided to more precisely control the cure speed and stability of the adhesive, as well as the molecular weight of the cured adhesive.
  • These additional inhibitors include those having aqueous pK a ionization constants ranging 2 to 8, preferably from 2 to 6, and most preferably from 2 to 5.
  • inhibitors include, but are not limited to, phosphoric acid (pK a 2.2), organic acids, such as acetic acid (pK a 4.8), benzoic acid (pK a 4.2), chloroacetic acid (pK a 2.9), cyanoacetic acid, and mixtures thereof.
  • organic acids such as acetic acid or benzoic acid.
  • the cyanoacrylate adhesive compositions described in this patent may also optionally contain a biocompatible plasticizer that may be any material that is soluble or dispersible in the cyanoacrylate composition, that increases the flexibility of the resulting polymeric film coating on the skin surface, and that, in the amounts employed, is compatible with the as measured by the lack of moderate to severe skin irritation it is substantially non-irritating (i.e., it is substantially non-irritating).
  • Suitable plasticizers are well known in the art and include those disclosed in U.S. Patent Nos. 2,784,127 and 4,444,933, which are incorporated herein by reference in their entirety.
  • plasticizers include, by way of example only, tributyl acetyl citrate, trihexyl acetyl citrate, butyl benzyl phthalate, dibutyl phthalate, dioctylphthalate, /.-butyryl t ⁇ -n- hexyl citrate, diethylene glycol dibenzoate, dimethyl sebacate, triethyl phosphate, tri(2- ethylhexyl)phosphate, tri(p-cresyl)phosphate, glyceryl triacetate, glyceryl tributyrate, diethyl sebacate, dioctyl adipate, isopropyl myristate, butyl stearate, lauric acid, trioctyl trimellitate, dioctyl glutarate, and mixtures thereof, and the like.
  • biocompatible plasticizer employed is not critical and preferred plasticizers include dioctylphthalate, tributyl acetyl citrate, and C -C -acyl tri- «-hexyl citrates.
  • suitable plasticizers include polymeric plasticizers, such as polyethylene glycol (PEG) esters and capped PEG esters or ethers, polyester glutarates and polyester adipates.
  • PEG polyethylene glycol
  • One particularly preferred class of plasticizers is dialkyl phthalates and, in particular, dioctyl phthalate, all of which are disclosed in U.S. Patent No.
  • the optional biocompatible plasticizer is present in an amount effective to increase flexibility of the resulting polymer film and in an amount that is substantially non-irritating.
  • the amount of plasticizer ranges from about 0.5 to about 30, or from about 10 to about 30 weight percent based on the total weight of the composition.
  • the amount of plasticizer ranges from about 15 to about 25 weight percent based on the total weight of the composition.
  • the plasticizing agent or agents may also be present in amounts ranging from about 0.5 wt. % to about 25 wt. %, or from about 1 wt. % to about 20 wt. % or from about 3 wt. % to about 15 wt. % or from about 5 wt. % to about 7 wt. %.
  • the biocompatible plasticizer is included.
  • the polymerizable cyanoacrylate adhesive optionally contains a thickening agent and may additionally contain one or more optional additives such as medicaments, colorants, perfumes, anti-diffusion agents, rubber modifiers, modifying agents, etc.
  • optional additives such as medicaments, colorants, perfumes, anti-diffusion agents, rubber modifiers, modifying agents, etc.
  • each of these optional additives should be both miscible and compatible with the cyanoacrylate composition and the resulting polymer.
  • Compatible additives are those that do not prevent the use of the cyanoacrylates in the manner described herein.
  • the optional thickening agent may be any biocompatible material that increases the viscosity of the composition.
  • suitable thickening agents include, by way of example, polymethyl methacrylate (PMMA) or other preformed polymers soluble or dispersible in the composition, a suspending agent such as fumed silica and the like with PMMA being preferred. Fumed and modified fumed silica are particularly useful in producing a gel for topical application having a viscosity of from about 1,500 to about 1,000,000 cSt at 20°C.
  • Suitable thickening agents for the compositions described herein also include a partial polymer of the alkyl cyanoacrylate as disclosed in U.S. Patent Nos.
  • Thickening agents are deemed to be biocompatible if they are soluble or dispersible in the composition and are compatible with the skin as measured by the lack of moderate to severe skin irritation.
  • concentration of thickening agent employed is preferably an amount sufficient to form a stable suspension or gel with the polymerizable cyanoacrylate ester composition. This, in turn, correlates with the viscosity of the composition.
  • stable suspensions are preferably achieved by addition of sufficient thickening agent to provide for a viscosity of from about 50 to 50,000 centipoise at 20°C.
  • the composition will comprise about 0.5 to about 10 percent by weight of the thickening agent based on the total weight of the composition wherein the composition will have a viscosity of about 50 to about 1,000,000 centipoise at 20°C.
  • colorants are added so that the polymer layer formed on the skin will contain a discrete and discernable color. Perfumes are added to provide a pleasant smell to the formulation.
  • Rubber modifiers are added to further enhance the flexibility of the resulting polymer layer.
  • Medicaments are added as necessary to achieve a desired prophylactic or therapeutic effect.
  • the amount of each of these optional additives employed in the composition is an amount necessary to achieve the desired effect.
  • Other medicaments suitable for use in conjunction with the cyanoacrylate composition include cortico steroids such as described by Greff, et al. in U.S. Patent No. 5,962,010, incorporated herein by reference in its entirety, and analgesic and/or anesthetic compounds such as lidocaine.
  • the former reduces inflammation at the tissue site whereas the latter reduces pain.
  • Combinations of steroids and analgesics are also suitable.
  • Specific cyanoacrylate adhesive compositions that may be used include but are not limited to the following: [0071] An n-butyl cyanoacrylate composition: A composition comprising fl-butyl cyanoacrylate, phenol, a blend of anionic and free radical inhibitors, and a plasticizer. [0072] In a preferred version of this composition, the amount of phenol is about 0.01% to about 5% of the total weight of the composition. In a more preferred version of this composition, the amount of phenol is about 0.1% to about 1.4%. In a more preferred version the phenol is present in about 0.1%, about 0.6%, or about 1% of the composition.
  • a blend of anionic and free radical inhibitors is employed.
  • the blend of anionic and free radical inhibitors comprises sulfur dioxide, and hydroquinone.
  • the blend of anionic and free radical inhibitors comprises sulfur dioxide, 4-methoxyphenol and hydroquinone.
  • the blend of anionic and free radical inhibitors contains a ppm amount of anionic inhibitor(s) and a ppm amount of free radical inhibitor(s) in a ratio of about 1:1 to about 1 :8, with ratios of about 1 : 1 and about 1 :4 being more preferred.
  • the blend of anionic and free radical inhibitors contains a ppm amount of sulfur dioxide and a ppm amount of hydroquinone in a ratio of about 1 : 1 to about 1 :4, with 1 : 1 and 1 :4 being the more preferred ratios.
  • the blend of anionic and free radical inhibitors contains a ppm amount of sulfur dioxide and a ppm amount of hydroquinone and a ppm amount of 4-methoxyphenol in a ratio of about 1:1:1 to about 1:4:4 (sulfur dioxide:hydroquinone:4-methoxyphenol) with ratios of about 1:1: and about 1:4:4 being more preferred.
  • the blend of anionic and free radical inhibitors contains either a blend of about 100 ppm of sulfur dioxide and about 400 ppm of hydroquinone or a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone.
  • the blend of anionic and free radical inhibitors contains either a blend of about 100 ppm of sulfur dioxide and about 400 ppm of hydroquinone and 400 ppm of 4-methoxyphenol or a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone and 400 ppm of 4-methoxyphenol.
  • the plasticizer is tributyl acetyl citrate or di-ethylhexyl phthalate.
  • the weight of plasticizer and weight of n-butyl cyanoacrylate are in a ratio of about 1:3 to about 1:4.
  • the plasticizer is either (1) tributyl acetyl citrate and the weight of plasticizer and weight of /.-butyl cyanoacrylate are in a ratio of about 1:4, or (2) di-ethylhexyl phthalate and the weight of plasticizer and weight of /.-butyl cyanoacrylate are in a ratio of about 1:3.
  • the amount of phenol is about 1% of the total weight of the composition
  • the blend of anionic and free > radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 400 ppm of hydroquinone and 400 ppm of 4-methoxyphenol
  • the plasticizer is tributyl acetyl citrate
  • the weight of plasticizer and weight of «-butyl cyanoacrylate are in a ratio of about 1 :4.
  • the amount of phenol is about 1% of the total weight of the composition
  • the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide, about 100 ppm of hydroquinone and 400 ppm of 4-methoxyphenol
  • the plasticizer is di-ethylhexyl phthalate
  • the weight of plasticizer and weight of /.-butyl cyanoacrylate are in a ratio of about 1 :3.
  • Blend of cyanoacrylate and decyl cyanoacrylate composition A composition comprising a blend of /.-butyl cyanoacrylate and decyl cyanoacrylate, phenol, a blend of anionic and free radical inhibitors, and an optional plasticizer.
  • the weight of /.-butyl cyanoacrylate and weight of decyl cyanoacrylate are present in a ratio of about 1 : 1 to about 3:7.
  • the amount of phenol is about 0.01% to about 5% of the total weight of the composition. In a more preferred version of this composition, the amount of phenol is about 0.1% to about 1.4%.
  • the phenol is present in about 0.1%, about 0.6%, or about 1% of the composition.
  • the blend of anionic and free radical inhibitors contains a blend of sulfur dioxide and hydroquinone.
  • the blend of anionic and free radical inhibitors contains a ppm amount of anionic inhibitor and a ppm amount of free radical inhibitor in a ratio of about 1:1.
  • the blend of anionic and free radical inhibitors contains a ppm amount of sulfur dioxide and a ppm amount of hydroquinone in a ratio of about 1:1.
  • the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone.
  • the optional plasticizer is absent.
  • the weight of .-butyl cyanoacrylate and weight of decyl cyanoacrylate are in a ratio of about 3:7, the amount of phenol is about 0.1% or about 0.6% of the total weight of the composition, the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone, and the plasticizer is absent.
  • Blend of decyl cyanoacrylate and ethoxyethyl cyanoacrylate composition A composition comprising a blend of decyl cyanoacrylate and ethoxyethyl cyanoacrylate, phenol, a blend of anionic and free radical inhibitors, and an optional plasticizer.
  • the weight of decyl cyanoacrylate and weight of ethoxyethyl cyanoacrylate are in a ratio of about 1 :1.
  • the amount of phenol is about 0.01% to about 5% of the total weight of the composition.
  • the amount of phenol is about 0.1% to about 1.4%. In a more preferred version the phenol is present in about 0.1%, about 0.6%, or about 1% of the composition.
  • the blend of anionic and free radical inhibitors contains a blend of sulfur dioxide and hydroquinone. In another preferred version of this composition, the blend of anionic and free radical inhibitors contains a ppm amount of anionic inhibitor and a ppm amount of free radical inhibitor in a ratio of about 1:1. In a more preferred version of the composition, the blend of anionic and free radical inhibitors contains a ppm amount of sulfur dioxide and a ppm amount of hydroquinone in a ratio of about 1:1.
  • the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone.
  • the optional plasticizer is absent.
  • the weight of decyl cyanoacrylate and weight of ethoxyethyl cyanoacrylate are in a ratio of about 1:1, the amount of phenol is about 0.1% or about 0.6% of the total weight of the composition, the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone, and the plasticizer is absent.
  • Blend ofn-butyl cyanoacrylate and octyl cyanoacrylate composition A composition comprising a blend of /--butyl cyanoacrylate and octyl cyanoacrylate, phenol, a blend of anionic and free radical inhibitors, and an optional plasticizer.
  • the weight of /?-butyl cyanoacrylate and weight of octyl cyanoacrylate are present in a ratio of about 1:1 to about 3:7.
  • the weight of /,-butyl cyanoacrylate and weight of octyl cyanoacrylate are present in a ratio of about 56:30.
  • the amount of phenol is about 0.01% to about 5% of the total weight of the composition. In a more preferred version of this composition, the amount of phenol is about 0.1% to about 1.4%. In a more preferred version the phenol is present in about 0.1%, about 0.6%, or about 1% of the composition.
  • the blend of anionic and free radical inhibitors contains a blend of sulfur dioxide and hydroquinone. In another preferred version of this composition, the blend of anionic and free radical inhibitors contains a ppm amount of anionic inhibitor and a ppm amount of free radical inhibitor in a ratio of about 1 : 1.
  • the blend of anionic and free radical inhibitors contains a ppm amount of sulfur dioxide and a ppm amount of hydroquinone in a ratio of about 1:1. In an even more preferred version of the composition, the blend of anionic and free radical inhibitors contains a blend of about 100 ppm of sulfur dioxide and about 100 ppm of hydroquinone. [0093] In another preferred version of this composition, the optional plasticizer is present in about 14 weight percent.
  • the methods of this invention comprise the in situ formation of an antimicrobial, cyanoacrylate polymer film on mammalian tissue such as mammalian skin.
  • the treatment protocol preferably involves tissue preparation prior to in situ formation of the cyanoacrylate polymer.
  • mammalian skin is first conventionally treated by cleaning with an appropriate antimicrobial composition.
  • the skin is preferably dried, e.g., blotted dry, and then an adherent antimicrobial polymeric film is formed over this site by applying a cyanoacrylate composition of this invention.
  • this composition comprises polymerizable cyanoacrylate monomers and/or reactive oligomers that, upon contact with the skin, polymerize in situ to form a polymeric film. Pretreatment of other mammalian tissue will also follow conventional procedures.
  • Polymerization occurs at ambient conditions for a sufficient period of time to allow robust films to form. In general, the particular length of time required for polymerization will vary depending on factors such as the amount of adhesive composition applied, the temperature of the tissue, the moisture content of the tissue, the surface area of tissue, and the like. However, in a preferred embodiment, polymerization is generally complete within about 10 to about 60 seconds while the tissue is maintained at ambient conditions; however, in some cases, polymerization can occur in as little as 5 seconds and up to about 5 minutes.
  • the tissue is maintained in a position that permits the cyanoacrylate to polymerize and form a polymeric film while minimizing any movement that might dislodge the cyanoacrylate from the tissue or create undesirable bonding.
  • Sufficient amounts of the composition are employed to cover (i.e., coat) the entire tissue site with a layer of the cyanoacrylate polymer. If necessary, excess cyanoacrylate monomer and/or oligomer can be removed with a wipe or tissue paper before polymerization or, after polymerization, any polymer formed at unintended sites can be removed with materials such as acetone.
  • the resulting polymeric film forms an antimicrobial, barrier film that strongly adheres to the skin and is both flexible and waterproof. Such strong adherence effectively eliminates the possibility that the film will separate from the tissue.
  • the polymeric film will only adhere to the skin for a period of about 1-4 days after which time it sloughs off. This occurs because the cyanoacrylate polymer is adhering only to the epidermal layer that is continuously in the process of being sloughed off and replaced by the underlying cells. Accordingly, the cyanoacrylate film need not be removed from such skin.
  • the polymeric film should be maintained in an unbroken manner over the entire tissue.
  • a second, preferably thinner, layer is applied thereto. Additional amounts of cyanoacrylate composition can be applied as needed to maintain an unbroken coating covering over the tissue.
  • the resulting polymeric film evidences improved durability in maintaining an unbroken film over the skin over time. In some cases, an unbroken film can be maintained on the skin up to 7 days after application without the need for reapplication. Similar results have been observed with the also preferred mixture of /.-butyl cyanoacrylate and decyl cyanoacrylate.
  • the polymeric film preferably has a thickness of no more than about 1 millimeter and, more preferably, the polymer layer has a thickness of from about 2 to about 500 microns and still more preferably from about 20 to about 100 microns. If thinner polymeric films are desired, then the polymeric film should have a thickness of from about 2 to about 50 microns and preferably from 10 to 40 microns. The amount of cyanoacrylate composition applied to a unit area to obtain such thicknesses is well within the skill of the art.
  • the size and thickness of the polymeric film formed onto the tissue area can be readily controlled by the amount and viscosity of cyanoacrylate adhesive composition packaged in a single dose product or by use of a multiple use dispenser that governs the amount of material applied onto a unit area of surface skin.
  • the dispenser described by Otake, U.S. Patent No. 4,958,748, which is incorporated by reference in its entirety, is one example of a dispenser that dispenses the cyanoacrylate adhesive composition in a controlled dropwise manner.
  • cyanoacrylate composition is stored at ambient conditions and can be provided in sterile form.
  • the cyanoacrylate adhesive compositions can be prepared by conventional methods of mixing the appropriate components until homogenous.
  • the adhesive compositions are generally prepared by mixing sufficient amounts of the various components, to achieve the effective concentration.
  • the viscosity of the composition is controlled by the nature and concentration of the cyanoacrylate ester, the presence and nature of the optional thickening agent or by the amount of any other material employed.
  • high viscosity compositions that employ lower concentrations of cyanoacrylate esters can be achieved by use of very high molecular weight oligomers. Such factors are well known in the art.
  • the concentration of polymerizable cyanoacrylate ester employed in the composition is preferably from about 50 to about 99.5 percent by weight based on the total weight of the composition, and more preferably from about 75 to about 89.5 percent by weight.
  • the concentration of phenol employed in the composition is sufficient to render the resulting polymeric film antimicrobial. That is to say that the concentration of phenol in the film is sufficient to ensure that the film exhibits antimicrobial activity when measured by conventional assays such as that described in Greff, et al. 9
  • the cyanoacrylate adhesive composition can be degassed. The degassing can be performed by any conventional degassing technique, i.e., thermal or vacuum treatment.
  • the resulting cyanoacrylate adhesive composition is optionally heat-sterilized and then stored, preferably in sealed vials until needed.
  • the cyanoacrylate adhesive composition is sterilized by dry heating the composition under conditions sufficient to sterilize the composition.
  • Other sterilization techniques can be used including, for example, electron beam sterilization, visible light irradiation, and the like. See, for example, U.S. Patent No. 6,248,800 which is incorporated herein by reference in its entirety.
  • the methods described herein are useful in forming an antimicrobial polymeric film over mammalian tissue.
  • This polymeric film finds particular utility in treating an existing bacterial infection at the tissue site or in inhibiting this tissue from becoming infected with bacteria.
  • Suitable mammals for use in these methods preferably include humans as well as domestic animals such as horses, cows, dogs, sheep, cats, etc.
  • Examples 1-4 below illustrate the advantageous features of the invention and Examples 5-7 illustrate how the methods of this invention could be practiced.
  • EXAMPLE 1 [0114] Seven antimicrobial agents taken from the FDA draft monograph for First Aid Products were evaluated for their compatibility with cyanoacrylate adhesives. The evaluation consisted of mixing the liquid or powdered solid at the recommended concentration directly into an ethyl cyanoacrylate composition and observing the reaction over 7 days. The ethyl cyanoacrylate composition was purchased from Parson International (Rochester, Michigan, USA) as Parfix 105 low viscosity and contains proprietary inhibitors that are believed to be hydroquinone and either sulfur dioxide or methane sulfonic acid. No other additional components were added except the antimicrobial agents. The tests were conducted at room temperature. If the mixture was stable for 7 days the set time of the mixture on skin was determined to ensure the mixture was capable of setting. TABLE 1
  • EXAMPLE 2 Three antimicrobial agents from Example 1, which are apparently compatible with cyanoacrylate adhesives, were tested to determine their aging properties when mixed in their "effective antimicrobial" concentrations in a composition containing 80% butyl cyanoacrylate, 20% tributyl acetyl citrate, and approximately 100 ppm of sulfur dioxide, 400 ppm of 4-methoxyphenol and 400 ppm of hydroquinone, and stored at 60°C.
  • the "effective antimicrobial" concentration means that amount determined using the FDA draft monograph for First Aid Products as having antimicrobial activity.
  • EXAMPLE 3 Three antimicrobial agents from Example 1, which are apparently compatible with cyanoacrylate adhesives, were tested to dete ⁇ nine their aging properties when mixed in their effective antimicrobial concentrations in a composition containing 80% butyl cyanoacrylate, 20% tributyl acetyl citrate, and approximately 100 ppm of sulfur dioxide and 400 ppm of hydroquinone, and stored under accelerated shelf-life conditions at 82°C. As before, the effective antimicrobial concentration was determined using the FDA draft monograph for First Aid Products.
  • EXAMPLE 4 [0120] In this example, three different polymerizable cyanoacrylate ester blends were tested. The blends used were (1) 30:70 w/w butyl cyanoacrylate: decyl cyanoacrylate, containing 100 ppm sulfur dioxide and 100 ppm hydroquinone; (2) 50:50 w/w decyl cyanoacrylate: ethoxyethyl cyanoacrylate containing 100 ppm sulfur dioxide and 100 ppm hydroquinone; and (3) 75:25 w/w butyl cyanoacrylate: di-ethylhexyl phthalate containing 100 ppm sulfur dioxide and 100 ppm hydroquinone.
  • the viscosity tends to increase and the solution will turn yellow and/or gray as the solution ages.
  • the shelf-life of a given composition can be approximated by measuring the viscosity, adhesion and set time of the adhesive compositions after storing the composition at elevated temperatures.
  • Table 4-6 show that the presence of phenol in either 0.1% or 0.6% increases the stability of polymerizable cyanoacrylate monomer compositions relative to compositions containing hexyl resorcinol as determined using viscosity and visual appearance as a metric.
  • the viscosity of the phenol containing compositions after 14 days at about 82°C were at least 50% less viscous than the control solution.
  • the adhesion and the set times of all the measured compositions have remained within acceptable and useful ranges.
  • EXAMPLE 5 A man subject to recurrent skin infections presents himself to the attending clinician with a large area of the inner right thigh that is beginning to redden and itch. The involved area and the surrounding two inches of skin are coated with a low viscosity liquid composition comprising 56% /.-butyl cyanoacrylate, 30% octyl cyanoacrylate, 14% tributyl acetyl citrate plasticizer (all percentages are weight percentages based on the total weight of the composition). Subsequently 5000 ppm phenol, 400 ppm hydroquinone, 400 ppm 4-methoxyphenol, and 150 ppm sulfur dioxide are added this mixture. The composition spreads easily and sets within 60 seconds to form a coherent flexible polymeric film.
  • EXAMPLE 6 A 13-year-old boy playing with ointments from the medicine cabinet causes a chemical bum on his left forearm by miss-using a depilatory cream. The approximately 2-inch diameter area is painful, red and swollen and the outer layer of skin is starting to peel off. The boy's mother thoroughly washes the skin and applies a film of antiseptic liquid bandage made from 80% /.-butyl cyanoacrylate, 20% tributyl acetyl citrate plasticizer (all percentages are weight percentages based on the total weight of the composition). Subsequently 0.5% by weight phenol, 150 ppm sulfur dioxide and 500 ppm hydroquinone are added to this mixture.
  • the liquid is applied as a thin film using a brush applicator in the bottle and sets within 30 seconds with only a mild stinging sensation. Once set, the pain of the burn is largely alleviated and the skin heals within 7 days, at which time the plastic film sloughs off.
  • EXAMPLE 7 An experienced cyclist loses traction and falls from his bike onto a wooden support while traversing a wet wooden bridge in a park. The fall leaves him with an extensive painful graze on his upper left arm. Because the park bridge is over a swampy area of land and is traversed by many domestic animals he is concerned about the risk of infection in the 6-inch by 3 -inch abrasion. He covers the abrasion with an antiseptic liquid bandage made from 60% //-butyl cyanoacrylate, 40% n-decyl cyanoacrylate (all percentages are weight percentages based on the total weight of the composition).

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  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
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  • Adhesives Or Adhesive Processes (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention porte sur des procédés et sur des formulations permettant de traiter ou prévenir des infections de tissus mammaliens tels que la peau. Les procédés de cette invention portent notamment sur la formation in situ d'un film polymère de cyanoacrylate contenant un phénol sur le tissu mammalien.
PCT/US2004/017573 2003-06-03 2004-06-02 Phenol antimicrobien contenant des compositions de cyanoacrylate WO2005000985A2 (fr)

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US60/475,857 2003-06-03
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102925064A (zh) * 2012-10-25 2013-02-13 无锡市三力胶带厂 一种介入性抗感染水性胶粘剂
WO2013064059A1 (fr) * 2011-11-02 2013-05-10 中国人民解放军军事医学科学院毒物药物研究所 Adhésif médical biodégradable et procédé de préparation et d'utilisation associé
WO2013033282A3 (fr) * 2011-09-02 2013-08-29 The Procter & Gamble Company Composition de soins personnels comprenant un composé d'hydroxyanisole butylé
EP2594247A3 (fr) * 2011-09-02 2015-01-07 The Procter & Gamble Company Composition de soins personnels comprenant un composé hydroxyanisole butylé
CN112999406A (zh) * 2021-02-25 2021-06-22 广州白云医用胶有限公司 一种抗癌医用胶及其制备方法和应用

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8110144B2 (en) * 2004-09-17 2012-02-07 Chemence Medical, Inc. Process for sterilization of and cyanoacrylate adhesives compositions and devices
US20070078207A1 (en) * 2005-09-30 2007-04-05 Jonn Jerry Y Stabilizer cyanoacrylate formulations
EP2022467A1 (fr) * 2007-08-07 2009-02-11 KPSS-Kao Professional Salon Services GmbH Composition à deux phases de conditionnement des cheveux
US8342765B2 (en) * 2008-06-12 2013-01-01 Advanced Medical Solutions (Plymouth) Limited Liquid applicator
WO2010088667A1 (fr) * 2009-02-02 2010-08-05 Niella Naidu Crèmes topiques améliorées
US10196543B2 (en) * 2011-03-31 2019-02-05 Adhezion Biomedical, Llc Fast bonding hair/eyelash extension adhesive compositions based on medical grade high viscosity cyanoacrylates
CN103205206B (zh) * 2012-01-16 2014-11-05 浙江久而久化学有限公司 一种磁材胶粘剂及其制备方法
EP2990796A1 (fr) 2014-08-29 2016-03-02 The Procter and Gamble Company Dispositif pour tester les propriétés de fibres de cheveux
GB2549975B (en) 2016-05-05 2022-04-13 Adv Med Solutions Ltd Liquid applicator
CN112584824B (zh) 2018-08-23 2024-03-29 新泰福托特股份有限公司 纳米颗粒
CN113318068A (zh) * 2021-06-21 2021-08-31 广州武州制药有限公司 氰基丙烯酸酯组合物及其制备方法、应用和透皮给药制剂
CN114796590A (zh) * 2022-04-26 2022-07-29 上海栗亮医疗科技有限公司 一种自增粘型氰基丙烯酸酯医用胶及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530037A (en) * 1993-12-23 1996-06-25 Loctite (Ireland) Limited Sterilized cyanoacrylate adhesive composition, and a method of making such a composition
US5998472A (en) * 1997-10-09 1999-12-07 Medlogic Global Corporation Mixed cyanoacrylate ester compositions
WO2001032795A1 (fr) * 1999-10-29 2001-05-10 Closure Medical Corporation Solutions de cyanoacrylate contenant des agents conservateurs
US6579916B1 (en) * 2000-11-21 2003-06-17 Medlogic Global Corporation Methods for sterilizing cyanoacrylate compositions
EP1508601A1 (fr) * 2003-08-21 2005-02-23 Closure Medical Corporation Compositions cyanoacryliques contenant un agent antimicrobien

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3654239A (en) * 1970-11-20 1972-04-04 Eastman Kodak Co Process for the preparation of poly-(alpha-cyanoacrylates)
US5306490A (en) * 1992-04-20 1994-04-26 Medlogic, Inc. Methods for retarding blister formation by use of cyanoacrylate adhesives
US5518730A (en) * 1992-06-03 1996-05-21 Fuisz Technologies Ltd. Biodegradable controlled release flash flow melt-spun delivery system
US6342213B1 (en) * 1992-06-09 2002-01-29 Medlogic Global Corporation Methods for treating non-suturable wounds by use of cyanoacrylate adhesives
US5254132A (en) * 1992-09-01 1993-10-19 Medlogic, Inc. Methods for treating suturable wounds by use of sutures and cyanoacrylate adhesives
US5328687A (en) * 1993-03-31 1994-07-12 Tri-Point Medical L.P. Biocompatible monomer and polymer compositions
US5403591A (en) * 1993-06-25 1995-04-04 Medlogic Global Corporation Methods for inhibiting skin ulceration by use of cyanoacrylate adhesives
US5653789A (en) * 1994-05-23 1997-08-05 Permagrain Products, Inc. Water base conditioner for acrylic wood flooring
US5580565A (en) * 1994-09-01 1996-12-03 Medlogic Global Corporation Use of cyanoacrylate adhesives for providing a protective barrier film for the skin
US5480935A (en) * 1994-09-01 1996-01-02 Medlogic Global Corporation Cyanoacrylate adhesive compositions
US5666817A (en) * 1996-12-10 1997-09-16 Edward R. Schulak Energy transfer system for refrigerator/freezer components
US5730994A (en) * 1997-01-10 1998-03-24 Medlogic Global Corporation Methods for draping surgical incision sites
US5684042A (en) * 1997-01-10 1997-11-04 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US6102205A (en) * 1997-10-08 2000-08-15 Medlogic Global Corporation Prepolymer compositions comprising an antimicrobial agent

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530037A (en) * 1993-12-23 1996-06-25 Loctite (Ireland) Limited Sterilized cyanoacrylate adhesive composition, and a method of making such a composition
US5998472A (en) * 1997-10-09 1999-12-07 Medlogic Global Corporation Mixed cyanoacrylate ester compositions
WO2001032795A1 (fr) * 1999-10-29 2001-05-10 Closure Medical Corporation Solutions de cyanoacrylate contenant des agents conservateurs
US6579916B1 (en) * 2000-11-21 2003-06-17 Medlogic Global Corporation Methods for sterilizing cyanoacrylate compositions
EP1508601A1 (fr) * 2003-08-21 2005-02-23 Closure Medical Corporation Compositions cyanoacryliques contenant un agent antimicrobien

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013033282A3 (fr) * 2011-09-02 2013-08-29 The Procter & Gamble Company Composition de soins personnels comprenant un composé d'hydroxyanisole butylé
EP2594247A3 (fr) * 2011-09-02 2015-01-07 The Procter & Gamble Company Composition de soins personnels comprenant un composé hydroxyanisole butylé
WO2013064059A1 (fr) * 2011-11-02 2013-05-10 中国人民解放军军事医学科学院毒物药物研究所 Adhésif médical biodégradable et procédé de préparation et d'utilisation associé
US9750841B2 (en) 2011-11-02 2017-09-05 Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. Biodegradable medical adhesive and preparation method and use thereof
CN102925064A (zh) * 2012-10-25 2013-02-13 无锡市三力胶带厂 一种介入性抗感染水性胶粘剂
CN112999406A (zh) * 2021-02-25 2021-06-22 广州白云医用胶有限公司 一种抗癌医用胶及其制备方法和应用

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